TY - JOUR

T1 - Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

AU - Lyskjær, Iben

AU - Davies, Christopher

AU - Strobl, Anna Christina

AU - Hindley, Joanna

AU - James, Steven

AU - Lalam, Radhesh K.

AU - Cross, William

AU - Hide, Geoff

AU - Rankin, Kenneth S.

AU - Jeys, Lee

AU - Tirabosco, Roberto

AU - Stevenson, Jonathan

AU - O’Donnell, Paul

AU - Cool, Paul

AU - Flanagan, Adrienne M.

AU - Genomics England Research Consortium

N1 - © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

PY - 2021/12

Y1 - 2021/12

N2 - Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.

AB - Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS.

KW - chondrosarcoma

KW - circulating tumour DNA

KW - GNAS

KW - IDH1

KW - IDH2

KW - prognosis

UR - http://www.scopus.com/inward/record.url?scp=85116431700&partnerID=8YFLogxK

U2 - 10.1002/1878-0261.13102

DO - 10.1002/1878-0261.13102

M3 - Journal article

C2 - 34528398

AN - SCOPUS:85116431700

VL - 15

SP - 3679

EP - 3690

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 12

ER -